Antibiotics are life-saving drugs, but their excessive application causes antimicrobial resistance. Another problem with antibiotics is the severe adverse effects of long-term treatment. Photopharmacological agents with molecular photoswitches could offer a solution to these problems, since the bioactivity of a drug could be controlled by light and only be activated when needed. However, the application of the photopharmacology currently relies mostly on UV light. With this approach, the drugs need to be activated before administration because of the toxicity and limited tissue penetration depth of UV light.
Wiktor Szymanski and Ben L. Feringa, University of Groningen, The Netherlands, and colleagues have developed diaminopyrimidines whose antibacterial activities against Escherichia coli can be controlled by visible light. The core structure of these compounds is that of the antibiotic trimethoprim. The team then used azobenzenes as photoswitches, connected either directly to the 2, 3, or 4 positions of the drug’s methoxyphenyl unit or introduced by alkylating the hydroxy group in the 4 position.
The researchers achieved a full control of antibacterial activity in the presence of bacteria using visible light for the first time. One of the diaminopyrimidines shows an eight-fold difference in activity before and after irradiation with red light. According to the team, these results are a step towards the in vivo control of photoswitchable antibiotics.
- Photocontrol of Antibacterial Activity: Shifting from UV to Red Light Activation,
Michael Wegener, Mickel J. Hansen, Arnold J. M. Driessen, Wiktor Szymanski, Ben L. Feringa,
J. Am. Chem. Soc. 2017, 139, 17979–17986.